LONG TERM GOAL: My proposed research seeks to assess the interrelationships between biliary bile acid & cholesterol, and plasma lipoprotein cholesterol & triglyceride, with particular emphasis on hepatic metabolism as it influences the catabolism of lipoprotein cholesterol and the association of bile acids and triglyceride during fed & fasting states in the normal BA- and lipoprotein-depleted animals. The baboon model allows ample opportunities to examine such interrelationships by determining hapatic uptake, release, and/or secretion of plasma lipoproteins, clearance from the extrasplanchnic (hepatic) region, and catabolism into bile. Assessment also includes the interrelations between plasma VLDL-TG with BAs and other lipoprotein components. With exteriorized but intact enterohepatic circulation and chronic indwelling (multiple) vascular catheters, a baboon model allows the simultaneous assessment of biliary bile acid, phospholipid, and cholesterol secretion and relative composition, and BA turnover with that of plasma lipoprotein metabolism by transgradient analysis (transplanchnic, transportal, and transhepatic gradients) during fed versus fasting state; intact versus interrupted EHC. VLDL-labelled TGFA will be used to assess VLDL-TG secretion and interaction with BAs in such states. These methods will therefore allow simultaneous assessment of lipoprotein and biliary lipid interaction in a primate model whose lipid metabolism is similar to that of man. In addition, total body exchangeable cholesterol may also be evaluated in these experiments where metabolic steady-states exist, while lipoprotein cholesterol and TG transfer (HDL, LDL, VLDL) will be followed during lipoprotein depletion (by plasmaphoresis). An attempt to cannulate mesenteric lymphatics will be done to study intestinal versus liver sources of lipoprotein lipids.